A cellular trafficking signal in the SIV envelope protein cytoplasmic domain is strongly selected for in pathogenic infection

The HIV/SIV envelope glycoprotein (Env) cytoplasmic domain contains a highly conserved Tyr-based trafficking signal that mediates both clathrin-dependent endocytosis and polarized sorting. Despite extensive analysis, the role of these functions in viral infection and pathogenesis is unclear. An SIV molecular clone (SIVmac239) in which this signal is inactivated by deletion of Gly-720 and Tyr-721 (SIVmac239ΔGY), replicates acutely to high levels in pigtail macaques (PTM) but is rapidly controlled. However, we previously reported that rhesus macaques and PTM can progress to AIDS following SIVmac239ΔGY infection in association with novel amino acid changes in the Env cytoplasmic domain. These included an R722G flanking the ΔGY deletion and a nine nucleotide deletion encoding amino acids 734–736 (ΔQTH) that overlaps the rev and tat open reading frames. We show that molecular clones containing these mutations reconstitute signals for both endocytosis and polarized sorting. In one PTM, a novel genotype was selected that generated a new signal for polarized sorting but not endocytosis. This genotype, together with the ΔGY mutation, was conserved in association with high viral loads for several months when introduced into naïve PTMs. For the first time, our findings reveal strong selection pressure for Env endocytosis and particularly for polarized sorting during pathogenic SIV infection in vivo

Regular Khat (Catha edulis) chewing is associated with elevated diastolic blood pressure among adults in Butajira, Ethiopia: A comparative study

<p>Abstract</p> <p>Background</p> <p>Fresh leaves and buds of the Khat plant (<it>Catha edulis</it>) contain Cathinone, an amphetamine like alkaloid responsible for its pharmacological action. Chewing of Khat has been associated with a transient rise in blood pressure and heart rate in experimental studies. Few studies examined the effect of regular or frequent Khat chewing on blood pressure at the population level. This study was conducted to examine the association of regular Khat chewing with blood pressure among adults.</p> <p>Methods</p> <p>We compared systolic and diastolic blood pressure of adults 35-65 years of age who reported regular chewing of Khat during the preceding five years to those who never chewed Khat during the same period. Study participants were recruited from purposively selected urban and rural villages of Butajira District in Ethiopia. The comparative groups, chewers (334) and non-chewers (330), were identified from among the general population through a house-to-house visit using a screening questionnaire. They were frequency-matched for sex and age within a five-year range. Data were collected through structured interviews and physical measurements including blood pressure, weight and height.</p> <p>Results</p> <p>The prevalence of hypertension was significantly higher among Khat chewers (13.4%) than non-chewers (10.7%), odds ratio (OR) = 1.66 (95% confidence interval (CI) 1.05, 3.13). A considerably high proportion of chewers (29.9%) than non-chewers (20.6%) had sub-optimal diastolic blood pressure (> 80 mmHg). The mean (sd) diastolic blood pressure was significantly higher among Khat chewers [75.0 (11.6)] than non-chewers [72.9 (11.7)], P < 0.05. Similarly, Khat chewers had significantly higher mean (sd) heart rate [76.3 (11.5)] than non-chewers [73.9 (12.6)], P < 0.05. There was no significant difference in mean systolic blood pressure between the two groups.</p> <p>Conclusion</p> <p>Regular chewing of Khat is associated with elevated mean diastolic blood pressure, which is consistent with the peripheral vasoconstrictor effect of Cathinone. Regular Khat chewing may have sustained effects on the cardiovascular system that can contribute to elevated blood pressure at the population level.</p

Allogeneic, off-the-shelf, SARS-CoV-2-specific T cells (ALVR109) for the treatment of COVID-19 in high-risk patients

Defects in T-cell immunity to SARS-CoV-2 have been linked to an increased risk of severe COVID-19 (even after vaccination), persistent viral shedding and the emergence of more virulent viral variants. To address this T-cell deficit, we sought to prepare and cryopreserve banks of virus-specific T cells, which would be available as a partially HLA-matched, off-the-shelf product for immediate therapeutic use. By interrogating the peripheral blood of healthy convalescent donors, we identified immunodominant and protective T-cell target antigens, and generated and characterized polyclonal virus-specific T-cell lines with activity against multiple clinically important SARS-CoV-2 variants (including ‘delta’ and ‘omicron’). The feasibility of making and safely utilizing such virus-specific T cells clinically was assessed by administering partially HLA-matched, third-party, cryopreserved SARS-CoV-2-specific T cells (ALVR109) in combination with other antiviral agents to four individuals who were hospitalized with COVID-19. This study establishes the feasibility of preparing and delivering off-the-shelf, SARS-CoV-2-directed, virus-specific T cells to patients with COVID-19 and supports the clinical use of these products outside of the profoundly immune compromised setting (ClinicalTrials.gov number, NCT04401410)

In vitro anti-HIV activity of some Indian medicinal plant extracts

Background Human Immunodeficiency Virus (HIV) persists to be a significant public health issue worldwide. The current strategy for the treatment of HIV infection, Highly Active Antiretroviral Therapy (HAART), has reduced deaths from AIDS related disease, but it can be an expensive regime for the underdeveloped and developing countries where the supply of drugs is scarce and often not well tolerated, especially in persons undergoing long term treatment. The present therapy also has limitations of development of multidrug resistance, thus there is a need for the discovery of novel anti-HIV compounds from plants as a potential alternative in combating HIV disease. Methods Ten Indian medicinal plants were tested for entry and replication inhibition against laboratory adapted strains HIV-1IIIB, HIV-1Ada5 and primary isolates HIV-1UG070, HIV-1VB59 in TZM-bl cell lines and primary isolates HIV-1UG070, HIV-1VB59 in PM1 cell lines. The plant extracts were further evaluated for toxicity in HEC-1A epithelial cell lines by transwell epithelial model. Results The methanolic extracts of Achyranthes aspera, Rosa centifolia and aqueous extract of Ficus benghalensis inhibited laboratory adapted HIV-1 strains (IC80 3.6–118 μg/ml) and primary isolates (IC80 4.8–156 μg/ml) in TZM-bl cells. Methanolic extract of Strychnos potatorum, aqueous extract of Ficus infectoria and hydroalcoholic extract of Annona squamosa inhibited laboratory adapted HIV-1 strains (IC80 4.24–125 μg/ml) and primary isolates (IC80 18–156 μg/ml) in TZM-bl cells. Methanolic extracts of Achyranthes aspera and Rosa centifolia, (IC801-9 μg/ml) further significantly inhibited HIV-1 primary isolates in PM1cells. Methanolic extracts of Tridax procumbens, Mallotus philippinensis, Annona reticulate, aqueous extract of Ficus benghalensis and hydroalcoholic extract of Albizzia lebbeck did not exhibit anti-HIV activity in all the tested strains. Methanolic extract of Rosa centifolia also demonstrated to be non-toxic to HEC-1A epithelial cells and maintained epithelial integrity (at 500 μg/ml) when tested in transwell dual-chamber. Conclusion These active methanolic extracts of Achyranthes aspera and Rosa centifolia, could be further subjected to chemical analysis to investigate the active moiety responsible for the anti-HIV activity. Methanolic extract of Rosa centifolia was found to be well tolerated maintaining the epithelial integrity of HEC-1A cells in vitro and thus has potential for investigating it further as candidate microbicide

A Latin American Perspective to Agricultural Ethics

The mixture of political, social, cultural and economic environments in Latin America, together with the enormous diversity in climates, natural habitats and biological resources the continent offers, make the ethical assessment of agricultural policies extremely difficult. Yet the experience gained while addressing the contemporary challenges the region faces, such as rapid urbanization, loss of culinary and crop diversity, extreme inequality, disappearing farming styles, water and land grabs, malnutrition and the restoration of the rule of law and social peace, can be of great value to other regions in similar latitudes, development processes and social problems. This chapter will provide a brief overview of these challenges from the perspective of a continent that is exposed to the consequences of extreme inequality in multiple dimensions and conclude by arguing for the need to have a continuous South-South dialogue on the challenges of establishing socially and environmentally sustainable food systems

A 5-year trend of Helicobacter pylori seroprevalence among dyspeptic patients at Bahir Dar Felege Hiwot Referral Hospital, Northwest Ethiopia

Meseret Workineh,1 Desalegn Andargie2 1Immunology and Molecular Biology, School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, 2University of Gondar Teaching Hospital, Gondar, Ethiopia Background: Helicobacter pylori infection is a major public health problem affecting half of the world&rsquo;s population. The prevalence of H. pylori varies in different societies and geographical locations. Thus, timely information on H. pylori epidemiology is critical to combat this infection. This study aimed to determine the seroprevalence and trend of H. pylori infection over a period of 5&nbsp;years among dyspeptic patients at Bahir Dar Felege Hiwot Referral Hospital, Northwest Ethiopia.Methods: A retrospective analysis of consecutive dyspeptic patients&rsquo; records covering the period between January 2009 and December 2013 was conducted. The hospital laboratory generated the data by a serological method of detecting the antibodies for H. pylori from serum by a one-step rapid test device. Chi-square analysis was used to identify significant predictors. A P-value of &lt;0.05 was considered as statistically significant.Results: Among all the study subjects, 2,733 (41.6%) were found to be seropositive. The seroprevalence was significantly higher in males (43.2%) than in females (39.9%) (&chi;2=9; P=0.002). In terms of age groups of the patients, high rates of H. pylori were found among the participants older than 60&nbsp;years (57%) (&chi;2=36.6; P&le;0.00001). The trend analysis of H. pylori prevalence revealed a fluctuating prevalence; it was 44.5% in the year 2009 and decreased to 34% and 40% in the years 2010 and 2011, respectively. However, there was an increment to 52.5% in the year 2012, and then it decreased to 30.2% in the year 2013.Conclusion: This study showed high seroprevalence of H. pylori among the dyspeptic patients in Bahir Dar Felege Hiwot Referral Hospital. The trend of the seroprevalence varied from year to year in the 5 consecutive years. Considering this, designing appropriate prevention and control strategies is mandatory. Keywords: H. pylori infection, dyspeptic patients, seroprevalence, Ethiopi

Seroprevalence of human immunodeficiency virus among voluntary counseling and testing clients at the University of Gondar Teaching Hospital, Northwest Ethiopia

Yohannes Sinku,1,2 Takele Gezahegn,1 Yalewayiker Gashaw,1 Meseret Workineh,1 Tekalign Deressa1 1School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, 2Diagnostic Laboratory Case Team, University of Gondar Teaching Hospital, Gondar, Ethiopia Background: The epidemiology of human immunodeficiency virus (HIV) infection in Ethiopia varies with regions, study population, and time. Thus, timely information on HIV epidemiology is critical for the combat of the epidemic. In this study, we aim to update HIV prevalence and risk factors among voluntary counseling and testing (VCT) clients at the University of Gondar Teaching Hospital, Northwest Ethiopia.Methods: A total of 2,120 VCT clients&rsquo; records from September 2007 to August 2010 were analyzed retrospectively. Bivariate logistic regression analysis was used to identify significant predictors. Odds ratio (OR) and 95% confidence intervals (CIs) were calculated. Statistical significance was set at P-value &lt;0.05.Results: Of 2,120 VCT clients, 363 (17.1%) were seropositive for HIV. A higher rate of HIV positivity was observed among female clients (20.4%) than that in male clients (14.0%) (OR 1.58, 95% CI 1.26&ndash;1.98, P=0.00). Widowed (95% CI 10.42&ndash;34.92, P=0.00), married (95% CI 3.42&ndash;5.94, P=0.00), divorced (95% CI 2.79&ndash;5.32, P=0.00), and illiterate (95% CI 2.33&ndash;5.47, P=0.00) clients were associated with HIV infection with the odds ratios of 19.07, 4.51, 3.85, and 3.57, respectively. Clients within the age category of 35&ndash;49&nbsp;years (OR 5.03, 95% CI 3.56&ndash;7.12, P=0.00) and above the age of 50&nbsp;years (OR 4.99, 95% CI 2.67&ndash;9.34, P=0.00) were more likely to be infected with HIV.Conclusion: HIV is still the major concern of public health in the Gondar area as evidenced by our data. Being female, widowed, married, illiterate, and older age were the identified risk factors for HIV infection. Thus, consideration of these factors in future intervention and clinical practice is recommended. Keywords: HIV, AIDS, voluntary counseling and testing, prevalence, Northwest Ethiopi

Modeling the effects of information-dependent vaccination behavior on meningitis transmission

We propose a mathematical model to investigate the effects of information–dependent vaccination behavior on meningitis transmission. The information is represented by means of information index as early proposed by d'Onofrio et al. (Theor. Popul. Biol., 2007). We perform a qualitative analysis based on stability theory, focusing to the global stability of the disease-free equilibrium (DFE) and the related transcritical bifurcation taking place at the threshold for the DFE. Finally, we assess the role of epidemiological and information parameters in the model dynamics through numerical simulations. Our simulations suggests that the impact of the parameters that are related to human behavior critically depend on the average information delay. For example, it can induce recurrent epidemics, provided that transfer rate from the carrier to the infectious state is over a threshold. Otherwise, the endemic equilibrium is (at least) locally stable

Immunological and hematological reference intervals among HIV-seronegative pregnant women in northwest Ethiopia

Meaza Genetu,1 Debasu Damtie,1 Meseret Workineh,1 Biniam Mathewos Tebeje,1,2 Bamlaku Enawgaw,3 Tekalign Deressa1 1Department of Immunology and Molecular Biology, School of Biomedical and Laboratory Sciences, College of Medicine and Health Science, University of Gondar, Gondar, Ethiopia; 2Molecular Parasitology Laboratory, Queensland Institute of Medical Research, Brisbane, Australia; 3Department of Hematology and Immunohematology, School of Biomedical and Laboratory Sciences, College of Medicine and Health Science, University of Gondar, Gondar, Ethiopia Background: Pregnancy is a state characterized by profound physiological hematological changes. However, hematological reference intervals being used in clinical practice in Ethiopia are derived from nonlocal general populations, despite the significant variations reported previously. The aim of this study was to determine the immunological and hematological reference intervals in healthy pregnancy among HIV-seronegative pregnant women in northwest Ethiopia.Materials and methods: A total of 200 healthy, HIV-seronegative pregnant women were enrolled from February 2015 to June 2015 in a cross-sectional study setting at Gondar University Hospital. Sociodemographic and obstetric data were collected using a structured questionnaire. Blood samples collected from each participant were used to define the immunological and hematological parameters. The mean, median, and 95% interval values were calculated for the immunological and hematological parameters. P-value &lt;0.05 was considered statistically significant for all variables.Results: This study found that there were changes in CD4+ T-cell count, platelet count, and hematocrit (HCT) values as pregnancy advances. The calculated combined reference intervals for the absolute CD4+ T-cell count and platelet count were 712.47&ndash;760.67 and 221.25&ndash;240.14, respectively. A progressive decline in the platelet count was observed as pregnancy advanced, with 95% intervals of 224.53&ndash;253.21, 209.50&ndash;237.38, and 213.70&ndash;247.86 in the first, second, and third trimesters, respectively (P=0.27). There was a statistically significant increase in mean (&plusmn;standard deviation [SD]) HCT with gestational age, being 39.18&plusmn;6.70, 41.96&plusmn;3.70, and 40.53&plusmn;3.77 in the first, second, and third trimesters, respectively (P=0.03). The overall 95% interval for hemoglobin (HB) concentration was 12.99&ndash;13.36&nbsp;g/dL, HCT 40.19%&ndash;41.49%, mean corpuscular volume (MCV) 93.33&ndash;94.63&nbsp;fL, and mean corpuscular hemoglobin (MCH) 28.88&ndash;34.81&nbsp;pg. Compared with the reference ranges derived from other studies, we found considerable variations in CD4+ T-cell count, HB, HCT, and MCV values.Conclusion: The findings of this study highlight the differences in immunohematological profile among pregnant women and nonpregnant women from Ethiopia and other countries, in addition to suggesting the need for such establishment of local reference values for different populations. Keywords: immunological parameter, hematological parameter, pregnant women, reference range, immunohematological reference intervals&nbsp